A number of new fluorous scavenging reagents have been developed and made commercially available by FTI.  Proof of concept for many of these products is provided in the following applications in the synthesis of chemical libraries.

Fluorous thiol has been used as a nucleophilic scavenger to remove a-bromoketone in the parallel synthesis of a tertiary amine library (Figure 1).  The quenched reaction mixture was washed with aqueous NH4Cl and then loaded onto a FluoroFlash® cartridge.  The product was collected in the 80-20 MeOH/H2O fraction and the scavenged species and excess thiol were collected in the 100% MEOH fraction.  The cartridge can be reused after a thorough wash with MeOH and acetone.  The aqueous work-up step can be avoided if a small amount of weak acidic ion exchange resin is added on top of the FluoroFlash® cartridge.  Both the base and the scavenged fluorous species can be retained on the cartridge.

Both isatoic anhydride and isocyanate have been introduced by FTI as electrophilic scavengers to remove primary and secondary amines in the synthesis of urea, thiourea and b-hydroxyamine analogs (Figure 2).

Very recently the Curran group introduced fluorous [1,2,4[triazoline-3,5-dione and fluorous benzylmaleimide as powerful scavengers to remove excess dienes, such as 1,2,3,4,5-pentamethylcyclopentakiene, anthracene, and 1,4-diphenyl-1,2-butadiene, from the Diels-Alder reaction mixture. After F-SPE, the Diels-Alder adducts are isolated in 77-99% yield and in 84-97% purity (Figure 3).

Selected References

1. Zhang, Wei. Fluorous Scavengers for Solution-Phase Synthesis The World Pharma Chem Directory 2003, 18-20.
2. Zhang, W.; Curran, D. P.; Chen, C. H. T. Use of fluorous silica gel to separate fluorous thiol quenching derivatives in solution-phase parallel synthesis, Tetrahedron 2002 , 58, 3871-3875.
3. Zhang, W; Hiu-Tung Chen, C; Nagashima, T. Fluorous electrophilic scavengers for solution-phase parallel synthesis Tetrahedron Letters 2003, 44, 2065-2068.
4. Werner, S.; Curran, D. Fluorous Dienophiles are Powerful Diene Scavengers in Diels-Alder Reactions Organic Letters 2003, 5, 3293-3296.